A novel synthetised sulphonylhydrazone coumarin (E)-4-methyl-N'-(1-(3-oxo-3H-benzo[f]chromen-2- yl)ethylidene)benzenesulphonohydrazide protect against isoproterenol-induced myocardial infarction in rats by attenuating oxidative damage, biological changes and electrocardiogram.

Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6-PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co-treated with 5,6-PhSHC or clopidogrel (150 µg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6-PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin-T (cTn-T), lactate dehydrogenase (LDH), and creatine kinase-MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6-PhSHC treatment. Results showed that injection of 5,6-PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL-c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6-PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric-acid-reactive substances (TBARS), when compared with ISO-induced rats. Taken together, these findings suggested a beneficial role for 5,6-PhSHC against ISO-induced MI in rats. Furthermore, in silico analysis showed that 5,6-PhSHC possess high computational affinities (E-value >-9.0 kcal/mol) against cyclooxygenase-2 (PDB-ID: 1CX2), vitamin K epoxide reductase (PDB-ID: 3KP9), glycoprotein-IIb/IIIa (PDB-ID: 2VDM) and catalase (PDB-ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction.

Allethrin Promotes Apoptosis and Autophagy Associated with the Oxidative Stress-Related PI3K/AKT/mTOR Signaling Pathway in Developing Rat Ovaries.

The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The present study was performed to investigate the developmental effects of the pyrethroid-based insecticide allethrin on ovarian function in rat offspring in adulthood. We mainly focused on the roles of oxidative stress, apoptosis, autophagy and the related pathways in ovarian injury. Thirty-day-old Wistar albino female rats were intragastrically administered 0 (control), 34.2 or 68.5 mg/kg body weight allethrin after breeding from Day 6 of pregnancy until delivery. We found that allethrin-induced ovarian histopathological damage was accompanied by elevations in oxidative stress and apoptosis. Interestingly, the number of autophagosomes in allethrin-treated ovaries was higher, and this increase was correlated with the upregulated expression of genes and proteins related to the autophagic marker LC-3. Furthermore, allethrin downregulated the expression of PI3K, AKT and mTOR in allethrin-treated ovaries compared with control ovaries. Taken together, the findings of this study suggest that exposure to the pyrethroid-based insecticide allethrin adversely affects both the follicle structure and function in rat offspring during adulthood. Specifically, allethrin can induce excessive oxidative stress and defective autophagy-related apoptosis, probably through inactivation of the PI3K/AKT/mTOR signaling pathway, and these effects may contribute to ovarian dysfunction and impaired fertility in female offspring.

Cardiopreventive capacity of a novel (E)-N'-(1-(7-methoxy-2-oxo-2H-chromen-3-yl) ethylidene)-4-methylbenzenesulfonohydrazide against isoproterenol-induced myocardial infarction by moderating biochemical, oxidative stress, and histological parameters.

This study is carried out to assess the cardiopreventive effect of (E)-N'-(1-(7-methoxy-2-oxo-2H-chromen-3-yl) ethylidene)-4-methylbenzenesulfonohydrazide or SHC, a novel synthesized coumarin, against myocardial infarction induced by isoproterenol (ISO). The SHC compound was identified and characterized by spectral methods (infrared, 1 H NMR [nuclear magnetic resonance], 13 C NMR, Nuclear Overhauser Effect Spectroscopy, and high-resolution mass spectroscopy). Male Wistar rats were divided into four groups: Control, ISO (rats were injected subcutaneously by 85 mg/kg body weight [BW] of isoproterenol at Days 6 and 7 of the experience), ISO + SHC (150 µg/kg BW, orally for 7 days) and ISO + acenocoumarol (150 µg/kg BW, orally for 7 days). Results showed that ISO induced a remarkable alteration of electrocardiogram (ECG) pattern and increases of plasma cardiac troponin T, creatine kinase-MB, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, lactate dehydrogenase, aspartate transaminase, and malondialdehyde. In addition, ISO reduced the high-density lipoprotein-cholesterol content and the activities of superoxide dismutase and glutathione peroxidase, with the induction of myocardial necrosis. However, SHC administration revealed a significant decrease in cardiac dysfunction markers, restored normal ECG pattern, as well as improving lipids parameters. Moreover, SHC treatment remarkably alleviated the cardiac oxidative stress and the myocardial remodeling process. Overall, the SHC offers good protection from acute myocardial infarction through the antioxidant capacity.

Potential effect of new (E)-4-hydroxy -N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide against acute myocardial infarction: Haemodynamic, biochemical and histological studies.

This study aimed to explore the cardioprotective effect of new synthesized coumarin (E)-4-hydroxy-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide denoted (Hyd.Cou) against myocardial infarction disorders. Male Wistar rats were divided into four groups; Control, isoproterenol (ISO), ISO + Acenocoumarol (Ac) and ISO + Hyd.Cou. Results showed that the ISO group exhibited serious alteration in EGC pattern, significant heart hypertrophy (+33%), haemodynamic disturbance and increase in plasma rate of CK-MB, LDH and troponin-T by 44, 53, and 170%, respectively, as compared to Control. Moreover, isoproterenol induced a rise in plasma angiotensin-converting enzyme activity (ACE) by 49%, dyslipidaemia, and increased thiobarbituric acid-reactive substances (TBARS) by 117% associated with decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 46% and 58%, respectively in myocardium. Interestingly, the molecular docking calculation demonstrated strong interactions of Hyd.Cou with the receptors of the protein disulphide isomerase (PDI) which could highlight the antithrombotic effect. Moreover, Hyd.Cou improved plasma cardiac dysfunction biomarkers, mitigated the ventricle remodelling process and alleviated heart oxidative stress damage. Overall, Hyd.Cou prevented the heart from the remodelling process through inhibition of ACE activity and oxidative stress improvement.

In vivo toxicities of the hospital effluent in Mahdia Tunisia.

Hospital effluent (HE) is one of the most important sources of pharmaceuticals released into the environment. This kind of pollution is a recognized problem for both human health and aquatic life. Consequently, in the present study, we assessed the effects of untreated hospital effluent on mice via biochemical and histopathological determinations. Female mice were given free access to water bottles containing untreated HE at different dilutions for 21 days. Then clinical biochemistry and histopathology evaluation were conducted. Serum biochemistry analysis showed the presence of significant increase in cholesterol, triglycerides, glycaemia and total bilirubin. However, phosphatase alkaline and urea activities have been significantly decreased compared to the control group. No significant variation was observed for the rest of the studied parameters (high-density lipoproteins; low-density lipoproteins and uric acid). Additionally, multiple alterations, including cellular necrosis, leucocyte infiltration and congestion, were observed in different tissues of mice exposed to the tested HE.

Permethrin induced arterial retention of native and oxidized LDL in rats by promoting inflammation, oxidative stress and affecting LDL receptors, and collagen genes.

This study is the first to examine the possible mechanism by which long-term exposure to permethrin (PER) can promote arterial retention of proatherogenic lipid and lipoproteins and related vascular dysfunction in rats. Experimental animals were administered two doses of oral PER, PER-1 (2.5 mg/kg/bw) and PER-2 (5 mg/kg/bw), for 90 consecutive days. The results indicated that both PER-1 and PER-2 increased plasmatic and aortic total cholesterol, low-density lipoprotein cholesterol (LDL-C), apo B-100, and oxidized LDL together with arterial scavenger LDL receptors (CD36) but markedly reduced plasmatic and hepatic high-density lipoprotein cholesterol and native LDL receptors in aortic and hepatic tissue. The levels of malondialdehyde, protein carbonyl, and reactive oxygen species were significantly higher, and glutathione content as well as catalase, superoxide dismutase, and glutathione peroxidase activities were suppressed in the aorta of the PER-1 and PER-2 groups. The arterial oxidative damage possibly caused by PER was clearly demonstrated by hematoxylin and eosin histological analysis. Moreover, PER treatment aggravated the inflammatory responses through enhancement of the production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-2, and interleukin-6) in both plasma and aorta. Furthermore, PER-1 and PER-2 potentiated the dysregulation of the aortic extracellular matrix (ECM) content by increasing mRNA activation of collagens I and III. The abundant histological collagen deposition observed in the media and adventitia of intoxicated rats using Masson's trichrome staining corroborates the observed change in ECM. These data showed that oxidative stress related to PER exposure increases the arterial accumulation of lipoprotein biomarkers, likely by actions on both LDL and CD36 receptors, together with the disruption of the aortic ECM.

High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats.

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-ß1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson's Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life.

The flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl, as a potential therapeutic agent for breast cancer with a promoting effect on ovarian function.

It is widely known that breast cancer cells eventually develop resistance to hormonal drugs and chemotherapies, which often compromise fertility. This study aimed to investigate the effect of the flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl (KARP), on 1) the viability of MCF-7 breast cancer cells and 2) ovarian function in rats. A dose-dependent decrease in MCF-7 cell survival was observed, and the IC50 value was found to be 48 µg/ml. Cells in the control group or those exposed to increasing concentrations of KARP experienced a similar generation of reactive oxygen species and induction of apoptosis. For the rats, estradiol levels correlated negatively to KARP dosages, although a recovery was obtained at administration of 30 mg/kg per day. Noteworthily, when compared against the control, this dosage led to significant increases in mRNA levels for CYP19, CYP17a, CCND2, GDF9, and INSL3 among the treatment groups, and ER1 and ER2 mRNA levels decreased in a dose-dependent manner. KARP shows great promise as an ideal therapy for breast cancer patients since it induced apoptosis and autophagy in cancerous cells without harming fertility in our animal model. Future investigations on humans are necessary to substantiate these findings and determine its efficacy as a general line of treatment.

HPLC-ESI-QTOF-MS/MS profiling and therapeutic effects of Schinus terebinthifolius and Schinus molle fruits: investigation of their antioxidant, antidiabetic, anti-inflammatory and antinociceptive properties.

The aim of the current work was to study the phytochemical variability among Schinus terebinthifolius (STE) and Schinus molle (SME) fruit extracts. The in vitro antioxidant, antihemolytic, antidiabetic, and macromolecule damage protective activities, as well as, the in vivo anti-inflammatory and antinociceptive capacities were assessed. Using the HPLC-ESI-QTOF/MS analysis, the chemical profile of fruit extract varied between S. terebinthifolius (30 compounds) and S. molle (16 compounds). The major compound was masazino-flavanone (5774.98 and 1177.65 µg/g sample for STE and SME, respectively). The investigations highlighted significant antioxidant proprieties when using ABTS radical (IC50; 0.12 and 0.14 mg/ml for STE and SME, respectively), superoxide (IC50; 0.17 and 0.22 mg/ml for STE and SME, respectively) and hydrogen peroxide (IC50; 014 and 0.17 mg/ml for STE and SME, respectively). In addition, STE and SME proved preventive effects against H2O2-induced hemolysis (IC50; 0.22 and 0.14 mg/ml for STE and SME, respectively). The in vitro antidiabetic effect revealed that STE and SME exhibited important inhibitory effects against α-amylase (IC50; 0.13 and 0.19 mg/ml for STE and SME, respectively) and α-glycosidase (IC50; 0.21 and 0.18 mg/ml for STE and SME, respectively) when compared with acarbose. Furthermore, the extracts showed potent inhibitory activity against AAPH-induced plasmid DNA damage, and protein oxidation. In vivo study revealed that STE and SME presented interesting antinociceptive and anti-inflammatory capacities. All observed effects highlighted the potential application of Schinus fruit extract in food and pharmaceutical industries against ROS-induced damage.

Zygophyllum album saponins prevent atherogenic effect induced by deltamethrin via attenuating arterial accumulation of native and oxidized LDL in rats.

The current study aimed to examine, for the first time, the relationship between exposure to deltamethrin (DLM) and atherogenic lipid profile disorders in adult Wistar rats, as well as, to verify the mechanism of the beneficial role of Zygophyllum album leaves extracts (ZALE). The experimental study was assessed using DLM (4 mg/kg b.w) either alone or co administered with ZALE (400 mg/kg b.w) orally for 90 days in rats. RP-HPLC-DAD-ESI-QTOF-MS was used to identify the bioactive metabolites present in ZALE. Plasmatic and aortic total cholesterol (TC), LDL-cholesterol (LDL-C), native LDL (LDL-apo B-100) and oxidized LDL (ox-LDL) were evaluated using auto-analyzer and a sandwich ELISA, respectively. The protein expressions of LDLR (native LDL receptor) and CD36 (Scavenger receptor class B) were evaluated in aorta or liver with a Western blot. The pathology has been confirmed with lipid stain (Oil Red O). Phytochemicals analysis revealed the presence of fifteen saponins in ZALE. Rats intoxicated with DLM revealed a significant increase in plasmatic and aortic lipid profile (TC, LDL-C, LDL-apo B-100 and ox-LDL), as well as, the concentration of the plasmatic cytokines include TNF-α, IL-2 and IL-6, compared to control. Hepatic native LDL and aortic CD36 receptor expression were increased in DLM treated group, however aortic LDL-R does not present any modification, when compared to control. The detected disturbances in lipid parameters were supported by Oil Red O applied. Due to their antioxidant activity, the bioactive compounds in ZALE as powerful agents able to prevent the pro-atherogenic effect observed in DLM-treated animals. These metabolites modulated most of inflammatory markers, prevented accumulation of lipid and lipoprotein biomarkers, regulated the major receptor regulators of hepatic cholesterol metabolism, as well as normalize lipid distribution in liver and aorta tissue.

Zygophyllum album leaves extract prevented hepatic fibrosis in rats, by reducing liver injury and suppressing oxidative stress, inflammation, apoptosis and the TGF-ß1/Smads signaling pathways. Exploring of bioactive compounds using HPLC-DAD-ESI-QTOF-MS/MS.

Zygophyllum album is traditionally used against many illnesses, such as liver disease. The present study investigated the bioactive compounds in methanol extract of Z. album (MEZA) using HPLC-DAD-ESI-QTOF-MS/MS and explored its possible antioxidative, anti-inflammatory, anti-apoptotic, and hepatoprotective effect. Twelve phenolic compounds were identified; isorhamnetin-3-O-rutinoside being the main one was the main composite (144.6 mg/100 g dm). Results showed that MEZA reduced significantly the biochemical markers (AST, ALT, LDH and ALP), and the hepatic oxidative stress indicators (MDA, PC, SOD, CAT, and GPx) in deltamethrin (DLM)-treated rats. Moreover, MEZA limited the inflammatory responses through downregulation of NF-κB gene, which suppressed the production of proinflammatory cytokines (TNF-α, IL-1ß, IL-6). Furthermore, Z. album reduced DLM-induced apoptosis by attenuating caspase 3 and p53 mRNA activation. MEZA treatment also alleviated upregulation of α-SMA, type I collagen, and TGF-ß1 mRNA in the liver. The possible antifibrotic effect of MEZA was clearly demonstrated by the histopathology examination, using Masson's Trichrome and Sirius Red stainings. Therefore, the current study suggested that the bioactive compounds of Z. album possessed antifibrotic effect against DLM-induced hepatic fibrosis, by protecting liver tissue, and inhibiting oxidative stress, inflammation, apoptosis and the TGF-ß1/Smads signaling pathways.

Cardioprotective effects of (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model.

The current study was carried out to evaluate the effect of pretreatment and co-treatment with a newly synthesized coumarin hydrazone, (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide (hereinafter EK6), against isoproterenol-induced myocardial infarction in rats. Changes in biochemistry, cardiac biomarkers, electrocardiography, and histopathology after treatment with EK6 or acenocoumarol (Sintrom) were studied. Animals were randomly divided into 4 groups: vehicle control (C), isoproterenol + Sintrom (ISO + Sin), isoproterenol + EK6 (ISO + EK6), and isoproterenol (ISO). Myocardial infarction was induced by subcutaneous ISO administration at a dose of 85 mg·kg-1·day-1 with a drug-free interval of 24 h on days 6 and 7. Treatment with ISO led to significant elevation (p < 0.05) in serum levels of cardiac injury biomarkers, namely cardiac troponin-T, lactate dehydrogenase, creatine kinase-MB, alanine aminotransferase, and aspartate aminotransferase compared with levels in the vehicle control. A change in the lipid profile was also observed as a significant increase in total cholesterol and triglycerides. Furthermore, ISO caused significant alterations in the electrocardiogram pattern, including significant ST-segment elevation, significant decreased R wave amplitude, and significant increase in heart rate (16%) as well as marked changes in the histopathology of the heart tissue. Pretreatment and co-treatment with newly synthesized coumarin hydrazone restored all ISO-induced biochemical, lipid, cardiac, and histopathological changes in rats with myocardial infarction.

HPLC-DAD identification of polyphenols from ethyl acetate extract of Amaranthus spinosus leaves and determination of their antioxidant and antinociceptive effects.

Amaranthus spinosus has been consumed traditionally to prevent various diseases including abdominal pain. In this study, the phytochemical composition, antioxidant and analgesic activities of an ethyl acetate extract of A. spinosus leaves (ASEA) were evaluated. The ASEA had the highest concentrations of total phenols (462.2 mg GAE/g DW), condensed tannin (5.01 mg CE/g DW) and total flavonoid contents (30.07 mg CE/g DW) compared to the chloroform, n-hexane, n-butanol and water extracts. Similarly, ASEA showed the most effective total antioxidant activity (45.45 µg/mL), DPPH scavenging activity (27.32 µg/mL) and hydrogen peroxide scavenging activity (30.60 µg/mL). ASEA with the doses of 200-600 mg/kg (p.o.) clearly demonstrated antinociceptive effects by reducing acetic acid-induced abdominal contortions with a maximal inhibition of 79.57% at 600 mg/kg and increasing latencies of the hot-plate paw-licking response. The tested doses also significantly (p < 0.001) decreased the reaction time in the formalin test at the neurogenic and inflammatory phases. ASEA contained ten polyphenols with caffeic acid being the predominant polyphenol. Overall, this study gave evidence that A. spinosus is a new antioxidant and analgesic agent, and justified its traditional use for the treatment of pain.

Effects of Rhus tripartitum fruit extract on CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats.

Rhus tripartitum D.C., Anacardiaceae, has traditionally been used in Tunisia against many illnesses. The present study investigates, for the first time, the protective effects of the methanol extract of Rhus tripartitum fruit (MERT) against CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicty in Wistar rats. ALT, AST, LDH, GGT, creatinin, urea, and uric acid levels were studied. The changes in antioxidant parameters such as malondialdehyde (MDA) and protein carbonyl contents were also determined. The increased levels of MDA (30.97 and 11.50 nmol MDA/mg protein in liver and kidney, respectively) and protein carbonyls (13.4 and 17.95 nmol/mg protein in liver and kidney, respectively) were attenuated by MERT pretreatment (19.35 and 6.1 nmol MDA/mg protein and 9.15 and 12 nmol/mg protein in liver and kidney, respectively). The MERT pretreatment significantly reduced the increased biochemical parameters of liver and kidney caused by CCl4 and cisplatin treatment. The histopathologic observation showed that MERT pretreatment restores the altered tissues. The observed results could be due to the high phenolic content and to MERT's important antioxidant potential. This study supports the hepatoprotective and nephroprotective effects of R. tripartitum.

Protective effects of Zygophyllum album extract against deltamethrin-induced hyperglycemia and hepato-pancreatic disorders in rats.

The current study was designed to investigate the possible mechanism involved in hyperglycemia induced by chronic exposure to deltamethrin (DLM) in rat and to assess whether this damage is amenable to modulation by Zygophyllum album. DLM, a synthetic pyrethroid pesticide, was administrated at a dose of 4 mg/kg body mass, during 60 days. Compared with control, DLM showed a significant increase of blood glucose (p ≤ 0.01) and glycosylated hemoglobin levels (p ≤ 0.01) and a clear decrease (p ≤ 0.01) of insulin and total hemoglobin levels. In addition, hepatic glycogen content and the activity of hexokinase decreased (p ≤ 0.01), whereas the activities of glucose-6-phosphatase and glycogen phosphorylase were significantly increased (p ≤ 0.01). Moreover, pancreatic lipid peroxidation (TBARS level) was higher (p ≤ 0.01) and oxidative stress biomarkers (SOD, CAT, GPx, and GSH) were altered owing to DLM toxicity. However, Z. album, when combined with DLM, significantly ameliorated almost all the hepato-pancreatic disorders induced by DLM alone. Furthermore, Z. album supplement was found to be effective in preserving the normal histological appearance of hepatic and pancreatic tissue. In conclusion, this study suggested that, owing to its antioxidant effects, methanolic extract of Z. album (MEZAL) can potentially prevent the hyperglycemia observed in DLM-treated group.

Electrospun Cactus Mucilage/Poly(vinyl alcohol) Nanofibers as a Novel Wall Material for Dill Seed Essential Oil (Anethum graveolens L.) Encapsulation: Release and Antibacterial Activities.

This study aimed to create long-lasting carriers by producing electrospun nanofibers loaded with dill seed (Anethum graveolens L.) essential oil (DSEO), using cactus mucilage (CM) and poly(vinyl alcohol) (PVA). Continuous and uniform electrospun nanofibers with a diameter of 158 ± 18 to 230 ± 26 nm were successfully made from the CM/PVA blend solution and the CM/PVA/DSEO emulsion. Atomic force microscopy topographic images revealed that the electrospun nanofibers had a tubular morphology. The thermogravimetric curves of DSEO, CM, pure PVA, and electrospun nanofibers demonstrate that the polymers used and the essential oil have effective chemical interactions. The water contact angle results suggest that the manufactured nanofibers are hydrophilic. CM/PVA consistently achieves a remarkable encapsulation efficiency of 100% DSEO. The electrospun nanofibers enabled the controlled release of free and encapsulated DSEO, resulting in sustained long-term release. The agar disk diffusion technique was used to study the antimicrobial activity of electrospun nanofibers and nanofibers containing DSEO against Gram-positive and Gram-negative bacteria. With a minimum inhibitory concentration of 2.5 mg/mL and a minimum bactericidal concentration of 5 mg/mL, electrospun nanofibers containing DSEO demonstrated bacteriostatic and bactericidal activities against foodborne pathogenic bacteria (Staphylococcus aureus and Pseudomonas aeruginosa). The DSEO-loaded electrospun nanofibers derived from carbohydrates show promise as an active interior coating for use in biomedical and food packaging applications.

Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts aqueous extract mitigates cisplatin-induced nephrotoxicity via attenuation of inflammation, and DNA damage.

Herein, we explored the protective effect of Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their O- and C-glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The in vivo results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that L. ocymifolia extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.

Grapevine Shoot Extract Rich in Trans-Resveratrol and Trans-ε-Viniferin: Evaluation of Their Potential Use for Cardiac Health.

A grapevine shoot extract (GSE) was obtained using ultrasound-assisted extraction and characterized. The main phenolic constituents were identified as stilbenoids. Among them, trans-resveratrol and trans-ε-viniferin stood out. The GSE was administered to an isoproterenol-induced myocardial injury animal model. The extract alleviated the associated symptoms of the administration of the drug, i.e., the plasma lipid profile was improved, while the disturbed plasma ion concentration, the cardiac dysfunction markers, the DNA laddering, and the necrosis of myocardial tissue were diminished. This effect could be related to the anti-oxidative potential of GSE associated with its antioxidant properties, the increased levels of endogenous antioxidants (glutathione and enzymatic antioxidants), and the diminished lipid peroxidative markers in the heart. The results also revealed angiotensin-converting enzyme (ACE)-inhibitory activity, which indicated the potential of GSE to deal with cardiovascular disease events. This work suggests that not only trans-resveratrol has a protective role in heart function but also GSE containing this biomolecule and derivatives. Therefore, GSE has the potential to be utilized in the creation of innovative functional ingredients.

Unlocking the hepatoprotective potential of the parasitic plant Orobanche foetida Poir. aqueous extract against CCl4-induced liver injury in rat.

In this current study, we explored the preventive capacity of the aqueous extract of Orobanche foetida (OF), a root holoparasite, against CCl4 prompt hepatotoxicity in rats. LC-MS/MS profiling revealed the existence of 32 compounds belonging to organic acids, benzoic acid derivatives, and hydroxycinnamic acids along with their glycosides and derivatives as well as several flavonoids. In vitro, OF demonstrated substantial antioxidant potential at DPPH and ABTS assays. Results showed that the pretreatment with OF for 6 weeks at the doses (25 mg/kg bw) and (50 mg/kg bw) countered the CCl4-induced liver injury by restoring liver injuries indicators (ALT, AST, LDH, ALP, GGT and bilirubin), normalizing lipid profile (TC, TG, LDL-C, and HDL-C), as well as, impeding DNA fragmentation. Furthermore, OF blocked the hepatic oxidative stress spurred by CCl4 administration through boosting antioxidant enzymes (GSH, CAT, and SOD) responsible of diminishing lipid peroxidation. exhibited an anti-inflammatory effect by downregulating TNF-α and IL-6 levels. OF suppressive effect on proinflammatory cytokines is further exerted by its capacity to modulate the expression of the NF-κB gene. In silico investigation revealed that among the 32 identified compounds, vanillic acid glucoside and dihydroxybenzoic acid glucoside have strong and stable bindings with the active sites of three key inflammatory proteins (PARP-1, TNF-α, IL-6), which could highlight the antioxidant and anti-inflammatory capacity of. Overall, this research provides a preliminary pharmacological support for the medicinal applications of Orobanche foetida for addressing inflammatory and hepato-pathological conditions.

Ephedra alata Seeds Confer Kidney Protection against Early Life Exposure to Acephate by Regulating Oxidative Insult and Activating Autophagy.

The aim of the current work was to examine for the first time the nephropreventive capacity of Ephedra alata seed extract (E) against maternal exposure to acephate in rat offspring. The in vivo results revealed that E. alata supplementation for 28 days (40 mg/kg b.w.) significantly attenuated the nephrotoxicity in adult offspring induced by acephate. In fact, it decreased the levels of creatinine and uric acid and increased the albumin content compared to the intoxicated group. The in utero studies showed that E. alata inhibited the renal oxidative stress generated by acephate exposure by reducing lipid peroxidation and enhancing antioxidant biomarker activities (GSH, CAT, and SOD). The inhibition of DNA fragmentation and the improvement of the ultrastructural changes highlighted the prophylactic effect of E. alata in renal tissue. Additionally, the immunofluorescence study showed the upregulation of LC3 gene expression, suggesting the capacity of E. alata extract to stimulate autophagic processes as a protective mechanism. Molecular docking analysis indicated that hexadecasphinganine, the major compound in E. alata, has a higher affinity toward the Na+/K+-ATPase, epithelial sodium channel (ENaC), and sodium hydrogen exchanger 3 (NHE3) genes than acephate. Hexadecasphinganine could be considered a potential inhibitor of the activity of these genes and therefore exerted its preventive capacity. The obtained findings confirmed that E. alata seed extract exerted nephropreventive capacities, which could be related to its bioactive compounds, which possess antioxidant activities.